Cancer Genomics & Proteomics最新文献

{"title":"DNA Methylation in Recurrent Glioblastomas: Increased TEM8 Expression Activates the Src/PI3K/AKT/GSK-3β/B-Catenin Pathway.","authors":"Paramita Kundu, Ruchi Jain, Nandaki Nag Kanuri, Arivazhagan Arimappamagan, Vani Santosh, Paturu Kondaiah","doi":"10.21873/cgp.20466","DOIUrl":"10.21873/cgp.20466","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastomas (GBM) are infiltrative malignant brain tumors which mostly recur within a year's time following surgical resection and chemo-radiation therapy. Studies on glioblastoma cells following radio-chemotherapy, have been demonstrated to induce trans-differentiation, cellular plasticity, activation of DNA damage response and stemness. As glioblastomas are heterogenous tumors that develop treatment resistance and plasticity, we investigated if there exist genome-wide DNA methylation changes in recurrent tumors.</p><p><strong>Materials and methods: </strong>Utilizing genome-wide DNA methylation arrays, we compared the DNA methylation profile of 11 primary (first occurrence) tumors with 13 recurrent (relapsed) GBM, to delineate the contribution of epigenetic changes associated with therapy exposure, therapy resistance, and relapse of disease.</p><p><strong>Results: </strong>Our data revealed 1,224 hypermethylated- and 526 hypomethylated-probes in recurrent glioblastomas compared to primary disease. We found differential methylation of solute carrier and ion channel genes, interleukin receptor/ligand genes, tumor-suppressor genes and genes associated with metastasis. We functionally characterized one such hypomethylated-up-regulated gene, namely anthrax toxin receptor 1/tumor endothelial marker 8 (ANTXR1/TEM8), whose expression was validated to be significantly up-regulated in recurrent glioblastomas compared to primary tumors and confirmed by immunohistochemistry. Using overexpression and knockdown approaches, we showed that TEM8 induces proliferation, invasion, migration, and chemo-radioresistance in glioblastoma cells. Additionally, we demonstrated a novel mechanism of β-catenin stabilization and activation of the β-catenin transcriptional program due to TEM8 overexpression via a Src/PI3K/AKT/GSK3β/β-catenin pathway.</p><p><strong>Conclusion: </strong>We report genome-wide DNA methylation changes in recurrent GBM and suggest involvement of the TEM8 gene in GBM recurrence and progression.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"485-501"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells.","authors":"Taira Hirose, Yuki Kunisada, Koichi Kadoya, Hiroki Mandai, Yumi Sakamoto, Kyoichi Obata, Kisho Ono, Hiroaki Takakura, Kazuhiro Omori, Shogo Takashiba, Seiji Suga, Soichiro Ibaragi","doi":"10.21873/cgp.20464","DOIUrl":"10.21873/cgp.20464","url":null,"abstract":"<p><strong>Background/aim: </strong>Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically.</p><p><strong>Results: </strong>Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models.</p><p><strong>Conclusion: </strong>This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"464-473"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of Matrix Metalloproteinase-2 Promoter Genotypes on Breast Cancer Risk.","authors":"Chih-Chiang Hung, Chung-Lin Tsai, Yu-Ting Chin, Yun-Chi Wang, Chia-Hua Liu, Meng-Liang Lin, Shih-Shun Chen, Jie-Long He, Chia-Wen Tsai, Chen-Hsien Su, DA-Tian Bau, Wen-Shin Chang","doi":"10.21873/cgp.20467","DOIUrl":"10.21873/cgp.20467","url":null,"abstract":"<p><strong>Background/aim: </strong>Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk.</p><p><strong>Materials and methods: </strong>MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls.</p><p><strong>Results: </strong>Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05).</p><p><strong>Conclusion: </strong>MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"502-510"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Worse Wilms' Tumor Outcomes Associated With Chemical Complementarity for Multiple T-Cell Receptor CDR3-CMV Epitope Pairs.","authors":"Kasey L Rigby, Michael J Diaz, Etienne C Gozlan, Dorottya B Kacsoh, Joanna J Song, Tabitha R Hudock, Andrea Chobrutskiy, Boris I Chobrutskiy, George Blanck","doi":"10.21873/cgp.20462","DOIUrl":"10.21873/cgp.20462","url":null,"abstract":"<p><strong>Background/aim: </strong>Wilms' tumors are pediatric renal tumors that generally have a good prognosis and outcomes. Viral illnesses have been linked to development of neoplasms and should be considered as a factor that could modulate overall survival.</p><p><strong>Materials and methods: </strong>We considered recently developed adaptive immune receptor, genomics and bioinformatics approaches to assess the potential impact of cytomegalovirus (CMV) infections in Wilms' tumor.</p><p><strong>Results: </strong>T-cell receptor (TCR) complementarity determining region-3 (CDR3) amino acid sequences from Wilms' tumor specimens represented by the Therapeutically Applicable Research to Generate Effective Treatments dataset were compared with known anti-CMV TCR CDR3s, indicating that cases representing the anti-CMV TCR CDR3s had worse outcomes. Then, a chemical complementarity scoring approach for the Wilms' tumor, TCR CDR3s and a series of CMV antigens further indicated that cases representing a higher chemical complementarity to the CMV antigens had worse outcomes.</p><p><strong>Conclusion: </strong>Overall, we present a potentially novel method to assess CMV infections and identify patients who could benefit from therapies that address such infections.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"439-447"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIK3CA Mutated Colorectal Cancers Without KRAS, NRAS and BRAF Mutations Possess Common and Potentially Targetable Mutations in Epigenetic Modifiers and DNA Damage Response Genes.","authors":"Ioannis A Voutsadakis","doi":"10.21873/cgp.20470","DOIUrl":"10.21873/cgp.20470","url":null,"abstract":"<p><strong>Background/aim: </strong>Despite therapeutic advancements, metastatic colorectal cancer is usually fatal, necessitating novel approaches based on the molecular pathogenesis to improve outcomes. Some colorectal cancers have no mutations in the extended RAS panel (KRAS, NRAS, BRAF) genes and represent a special subset, which deserves particular therapeutic considerations.</p><p><strong>Materials and methods: </strong>The genomic landscape of colorectal cancers from publicly available genomic series was interrogated, using the cBioportal platform. Colorectal cancer cohorts with cancers devoid of KRAS/NRAS or BRAF mutations were evaluated for the presence of mutations in the catalytic sub-unit alpha of kinase PI3K, encoded by the gene PIK3CA.</p><p><strong>Results: </strong>PIK3CA mutations in the absence of KRAS/NRAS/BRAF mutations were observed in 3.7% to 7.6% of colorectal cancers in the different series examined. Patients with all four genes in wildtype configuration (quadruple wild type) represented 32.2% to 39.9% of cases in the different series examined. Compared with quadruple wild type cancers, triple (KRAS/NRAS/BRAF) wild type/PIK3CA mutated cancers had a higher prevalence of high TMB cases and additional mutations in colorectal cancer associated genes except for mutations in TP53. Mutations in genes encoding for epigenetic modifiers and the DNA damage response (DDR) were also more frequent in triple wild type/PIK3CA mutated cancers. The prognosis of the two groups was comparable.</p><p><strong>Conclusion: </strong>Colorectal cancers with PIK3CA mutations in the absence of KRAS/NRAS/BRAF mutations have frequently mutations in epigenetic modifiers and DDR response genes, which may provide opportunities for targeting. These mutations are present in a smaller subset of quadruple wild type cancers.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"533-548"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical and Genetic Landscape of Hereditary Cancer: Experience from a Single Clinical Diagnostic Laboratory.","authors":"Nikolaos Tsoulos, Konstantinos Agiannitopoulos, Kevisa Potska, Anastasia Katseli, Christina Ntogka, Georgia Pepe, Dimitra Bouzarelou, Athanasios Papathanasiou, Dimitrios Grigoriadis, Georgios N Tsaousis, Helen Gogas, Theodore Troupis, Konstantinos Papazisis, Ioannis Natsiopoulos, Vassileios Venizelos, Kyriakos Amarantidis, Stylianos Giassas, Christos Papadimitriou, Elena Fountzilas, Maroulio Stathoulopoulou, Anna Koumarianou, Grigorios Xepapadakis, Alexandru Blidaru, Daniela Zob, Oana Voinea, Mustafa Özdoğan, Mahmut Çerkez Ergören, Alinta Hegmane, Eirini Papadopoulou, George Nasioulas, Christos Markopoulos","doi":"10.21873/cgp.20463","DOIUrl":"10.21873/cgp.20463","url":null,"abstract":"<p><strong>Background/aim: </strong>The application of next-generation sequencing (NGS) technology in the genetic investigation of hereditary cancer is important for clinical surveillance, therapeutic approach, and reducing the risk of developing new malignancies. The aim of the study was to explore genetic predisposition in individuals referred for hereditary cancer.</p><p><strong>Materials and methods: </strong>A total of 8,261 individuals were referred for multigene genetic testing, during the period 2020-2023, in the laboratory, and underwent multigene genetic testing using NGS. Among the examined individuals, 56.17% were diagnosed with breast cancer, 6.77% with ovarian cancer, 2.88% with colorectal cancer, 1.91% with prostate cancer, 6.43% were healthy with a significant family history of cancer, while 3.06% had a different type of cancer and 0.21% had not provided any information. Additionally, in 85 women with breast cancer we performed whole exome sequencing analysis.</p><p><strong>Results: </strong>20% of the examined individuals carried a pathogenic variant. Specifically, 54.8% of the patients had a pathogenic variant in a clinically significant gene (BRCA1, BRCA2, PALB2, RAD51C, PMS2, CDKN2A, MLH1, MSH2, TP53, MSH6, APC, RAD51D, PTEN, RET, CDH1, MEN1, and VHL). Among the different types of pathogenic variants detected, a significant percentage (6.52%) represented copy number variation (CNV). With WES analysis, the following findings were detected: CTC1: c.880C>T, p.(Gln294*); MLH3: c.405del, p.(Asp136Metfs*2), PPM1D: c.1426_1430del, p.(Glu476Leufs*3), and SDHB: c.395A>G, p.(His132Arg).</p><p><strong>Conclusion: </strong>Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants' carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"448-463"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of the DNA-Repair Gene POLQ only in BRCA1-mutant Breast-Cancer Cells by Methionine Restriction.","authors":"Tomonari Kunihisa, Sachiko Inubushi, Hirokazu Tanino, Robert M Hoffman","doi":"10.21873/cgp.20458","DOIUrl":"10.21873/cgp.20458","url":null,"abstract":"<p><strong>Background/aim: </strong>BRCA1/2 mutations in breast cancer cells impair homologous recombination and promote alternative end joining (Alt-EJ) for DNA-damage repair. DNA polymerase theta, encoded by POLQ, plays a crucial role in Alt-EJ, making it a potential therapeutic target, particularly in BRCA1/2-mutant cancers. Methionine restriction is a promising approach to target cancer cells due to their addiction to this amino acid. The present study investigated the expression of POLQ in BRCA1/2 wild-type and BRCA1-mutant breast cancer cells under methionine restriction.</p><p><strong>Materials and methods: </strong>POLQ mRNA expression was measured using qRT-PCR in BRCA1/2 wild-type (MDA-MB-231) and BRCA1- mutant (HCC1937 and MDA-MB-436) breast-cancer cells under normal, or serum-restricted, or serum- and methionine-restricted conditions.</p><p><strong>Results: </strong>Compared to BRCA1/2 wild-type cells, BRCA1-mutant cells displayed significantly higher basal POLQ expression in normal medium. Methionine restriction further increased POLQ expression in the BRCA1-mutant cells but decreased it in the BRCA1/2 wild-type cells.</p><p><strong>Conclusion: </strong>The present findings suggest that methionine restriction showed differential effects on POLQ expression, potentially impacting Alt-EJ activity, in BRCA1/2 wild-type and BRCA1-mutant breast-cancer cells. Further investigation is needed to explore the potential of combining methionine restriction with DNA-repair inhibitors, such as PARP inhibitors, to overcome drug resistance in BRCA1/2 mutant cancers.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"399-404"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARHGAP29 Is Involved in Increased Invasiveness of Tamoxifen-resistant Breast Cancer Cells and its Expression Levels Correlate With Clinical Tumor Parameters of Breast Cancer Patients.","authors":"Maike Kansy, Katharina Wert, Katharina Kolb, Julia Gallwas, Carsten Gründker","doi":"10.21873/cgp.20454","DOIUrl":"10.21873/cgp.20454","url":null,"abstract":"<p><strong>Background/aim: </strong>Aggressive breast cancer (BC) cells show high expression of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. In breast cancer cells in which mesenchymal transformation was induced, ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression increased significantly. Therefore, we investigated whether there is a correlation between expression of ARHGAP29 and tumor progression in BC. Since tamoxifen-resistant BC cells exhibit increased mesenchymal properties and invasiveness, we additionally investigated the relationship between ARHGAP29 and increased invasion rate in tamoxifen resistance. The question arises as to whether ARHGAP29 is a suitable prognostic marker for the progression of BC.</p><p><strong>Materials and methods: </strong>Tissue microarrays were used to investigate expression of ARHGAP29 in BC and adjacent normal breast tissues. Knockdown experiments using siRNA were performed to investigate the influence of ARHGAP29 and the possible downstream actors RhoC and pAKT1 on invasive growth of tamoxifen-resistant BC spheroids in vitro.</p><p><strong>Results: </strong>Expression of ARHGAP29 was frequently increased in BC tissues compared to adjacent normal breast tissues. In addition, there was evidence of a correlation between high ARHGAP29 expression and advanced clinical tumor stage. Tamoxifen-resistant BC cells show a significantly higher expression of ARHGAP29 compared to their parental wild-type cells. After knockdown of ARHGAP29 in tamoxifen-resistant BC cells, expression of RhoC was significantly reduced. Further, expression of pAKT1 decreased significantly. Invasive growth of three-dimensional tamoxifen-resistant BC spheroids was reduced after knockdown of ARHGAP29. This could be partially reversed by AKT1 activator SC79.</p><p><strong>Conclusion: </strong>Expression of ARHGAP29 correlates with the clinical tumor parameters of BC patients. In addition, ARHGAP29 is involved in increased invasiveness of tamoxifen-resistant BC cells. ARHGAP29 alone or in combination with its downstream partners RhoC and pAKT1 could be suitable prognostic markers for BC progression.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"368-379"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of PD-L1 Is Increased by Methionine Restriction Using Recombinant Methioninase in Human Colorectal Cancer Cells.","authors":"Kohei Mizuta, Byung Mo Kang, Qinghong Han, Yutaro Kubota, Sei Morinaga, Motokazu Sato, Michael Bouvet, Yasunori Tome, Kotaro Nishida, Robert M Hoffman","doi":"10.21873/cgp.20457","DOIUrl":"10.21873/cgp.20457","url":null,"abstract":"<p><strong>Background/aim: </strong>It has been recently demonstrated that a methionine-restricted diet increases the response to immune checkpoint inhibitors (ICIs) via an increase in PD-L1 in a syngeneic mouse colorectal-cancer model. Our laboratory has developed recombinant methioninase (rMETase) to restrict methionine. The aim of the present study was to determine if rMETase can increase PD-L1 expression in a human colorectal cancer cell line in vitro.</p><p><strong>Materials and methods: </strong>We evaluated the half-maximal inhibitory concentration (IC₅₀) value of rMETase on HCT-116 human colorectal cancer cells. HCT-116 cells were treated with rMETase at the IC₅₀ Western immunoblotting was used to compare PD-L1 expression in HCT-116 cells treated with and without rMETase.</p><p><strong>Results: </strong>The IC₅₀ value of rMETase on HCT-116 was 0.79 U/ml. Methionine restriction using rMETase increased PD-L1 expression compared to the untreated control (p<0.05).</p><p><strong>Conclusion: </strong>Methionine restriction with rMETase up-regulates PD-L1 expression in human colorectal cancer cells and the combination of rMETase and ICIs may have the potential to improve immunotherapy in human colorectal cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"395-398"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of Oxygen Enhanced Magnetic Resonance Imaging (OE-MRI) and a Pilot Genomic Study of Hypoxia in Bladder Cancer Xenografts.","authors":"Rekaya Shabbir, Brian A Telfer, Ben Dickie, Mark Reardon, Muhammad Babur, Kaye Williams, Catharine M L West, Ananya Choudhury, Tim A D Smith","doi":"10.21873/cgp.20455","DOIUrl":"10.21873/cgp.20455","url":null,"abstract":"<p><strong>Background/aim: </strong>Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery.</p><p><strong>Materials and methods: </strong>The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm³) or large (700 mm³) tumours were imaged, breathing air then 100% O₂, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N₂, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays.</p><p><strong>Results: </strong>Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour.</p><p><strong>Conclusion: </strong>OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"380-387"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}